Introduction

Suzetrigine is an oral, selective sodium channel blocker and non-opioid analgesic that is used to treat moderate or severe pain. Suzetrigine is typically given for only a few days and has not been linked to elevations in serum aminotransferase or alkaline phosphatase levels during therapy or to episodes of clinically apparent liver injury.

Background

Suzetrigine (soo ze’ tri geen) is a non-opioid analgesic that is used to treat moderate or severe pain such as occurs after surgery. Its mechanism of action appears to be based on selective blockage of a sodium channel Na_V1.8 which is expressed on peripheral sensory neurons but not in the brain or spinal cord. By stabilizing the sodium channel in a closed state, suzetrigine inhibits action potentials that act as pain signals to the central nervous system. Importantly, suzetrigine has not been shown to cause addiction, dependence, sedation, or somnolence. In preregistration double blind, placebo- and active comparator-controlled trials, suzetrigine was more effective in reducing pain than placebo and similar in efficacy to standard therapy with the combination of hydrocodone and acetaminophen. Based upon these studies, suzetrigine was approved in 2025 by the FDA in the United States as therapy for moderate to severe acute pain in adults. Suzetrigine is available in tablets of 50 mg under the brand name Journavx. The recommended dose is 100 mg initially followed by 50 mg every 12 hours for the shortest duration possible for pain control and generally not to exceed 14 days. Common adverse events include mild to moderate itching, muscle spasms, rash, and increases in serum creatine phosphokinase (CPK) levels. Use of suzetrigine should be avoided in patients with advanced, decompensated liver disease (Child-Pugh C) and lower doses are recommended in patients with early decompensated disease (Child-Pugh B).

Hepatotoxicity

In the prelicensure trials of suzetrigine, rates of serum aminotransferase elevations during suzetrigine therapy were less than 1% and were generally similar or slightly less than in patients receiving placebo or the combination of acetaminophen and hydrocodone, an active standard regimen of pain control. There were only rare ALT or AST elevations above 5 times the upper limit of normal (ULN) and no elevations of ALT or AST accompanied by jaundice or symptoms. In other uncontrolled studies of suzetrigine used for up to 14 days for both surgical and non-surgical pain, there were no instances of clinically apparent or life-threatening cases of liver injury. Since approval and clinical availability of suzetrigine, there have been no published case reports of clinically apparent liver injury, but clinical experience with its use has been limited.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Suzetrigine has not been linked to serum aminotransferase, alkaline phosphatase or bilirubin elevations during therapy although clinical experience with its use for more than a few days is limited. Suzetrigine is metabolized in the liver largely via CYP 3A4 and is susceptible to drug-drug interactions with CYP 3A4 inducers or inhibitors, concurrent administration of which should be avoided. Suzetrigine may interfere with the metabolism of other CYP 3A4 substrates and may also lower hormonal contraceptive levels.

Outcome and Management

The product label does not recommend monitoring of liver tests before or during suzetrigine therapy. De novo appearance of liver test abnormalities or evidence of liver injury during therapy should lead to its discontinuation until the cause of the abnormalities is identified. There is no information on cross reactivity in risk for adverse events, hypersensitivity, or hepatic injury between suzetrigine and other analgesics such as acetaminophen, nonsteroid anti-inflammatory agents, or opiates.

Drug Class: Analgesics

Other agents for moderate to severe pain: Nonsteroidal Antiinflammatory Drugs (NSAIDs),

Acetaminophen, Opioids, Opioid Antagonists